A novel O2-phase Li1.033Ni0.2[□0.1Mn0.5]O2 cathode with native vacancies (denoted as "□") was delicately designed. By a combination of noninvasive 7Li pj-MATPASS NMR and electron paramagnetic resonance measurements, it is unequivocally shown that the reservation of native vacancies enables the fully reversible local structural transformation without the formation of Li in the Li layer (Litet) in Li1.033Ni0.2[□0.1Mn0.5]O2 during the initial and subsequent cycling. In addition, the pernicious in-plane Mn migration that would result in the generation of trapped molecular O2 is effectively mitigated in Li1.033Ni0.2[□0.1Mn0.5]O2. As a result, the cycle stability of Li1.033Ni0.2[□0.1Mn0.5]O2 is significantly enhanced compared to that of the vacancy-free Li1.033Ni0.2Mn0.6O2, showing an extraordinary capacity retention of 102.31% after 50 cycles at a rate of 0.1C (1C = 100 mA g-1). This study defines an efficacious strategy for upgrading the structural stability of O2-type Li-rich layered oxide cathodes with reversible high-voltage anion redox activity.